Nonirritating nonionic tissue cleaning compositions

ABSTRACT

A nonirritating, nonionic detergent surfactant composition suitable for application to and cleaning of sensitive tissue, including periocular and ocular tissue, having a low cytotoxicity and high cleaning ability includes a principal nonionic surfactant and at least one auxiliary nonionic surfactant present in the surfactant composition in sufficient amounts to increase the cleaning ability of the principal nonionic surfactant.

This application is a divisional application of Ser. No. 08/074,318,filed Jun. 9, 1993, now allowed, which is the continuation of Ser. No.07/819,139, filed Jan. 10, 1992, now U.S. Pat. No. 5,252,246.

The present invention generally relates to detergent surfactantcompositions suitable for application to and cleaning of sensitivetissues. More particularly, the present invention relates tonon-irritating detergent surfactant compositions, comprised of acombination of nonirritating surfactants, especially suitable for lidhygiene in the treatment of chronic blepharitis.

The blepharitis, or inflammation of the eyelid, is a frequentlyencountered ocular disease. In addition to causing red and itching eyes,blepharitis may also interfere with the fitting of contact lenses, aswell as aggravate the treatment of keratitis sicca, endanger intraocularsurgery, or lead to corneal complications, such as toxic ephithealkeratitis catarrhal ulceration or phlycetnlosis.

One common symptom of blepharitis is a heavy deposition of oily debriscalled scurf on the eyelashes and lid margins. The oily debris is thesecretion (meibum) of meibomian glands. In the blepharitis patients, itis often found that their meibomian glands suffer from oversecretionand/or a thickened meibum. As a result, the glands are engorged, cloggedand inflamed.

The meibum is composed of various classes of lipids including a fattywax/sterol ester fraction of up to sixty percent. This lipid componentcan enhance the accumulation of debris and crusting which furtherexacerbates inflammation associated with the blepharitis.

Lid hygiene is currently the most accepted treatment for blepharitis. Inaddition, a number of oral and topical medications may be utilized toaugment the primary lid hygiene therapy as may be prescribed on anindividual basis. Effective cleaning agents for removal of meibomiansecretions associated with debris have been anionic surfactants havinghigh foaming characteristics. See, for example, U.S. Pat. No. 5,000,868.

Unfortunately, such anionic surfactants tend to be irritating tosensitive ocular tissue and because of their ionic nature, may bechemically incompatable with other formulation ingredients such as, forexample, buffers, preservatives and medicaments.

Consequently, surfactant compositions, specifically formulated for lidhygiene, have required the presence of surfactants capable of reducingthe irritant properties of the anionic surfactant or reducing theirchemical incompatability.

The composition of the present invention, effective for use onperiocular and ocular surface tissues includes no component necessaryfor reducing irritating characteristics of other surfactant components.

SUMMARY OF THE INVENTION

The present invention is a nonirritating detergent surfactantcomposition suitable for application to and cleaning of sensitivetissues which is especially effective for cleaning of ocular andperiocular tissue.

The composition comprises a principal nonionic surfactant present in thenonirritating detergent surfactant composition in a sufficient amount toclean the sensitive tissue. More particularly, the cleaning ability maybe defined in terms of the lipid cleaning efficiency of the surfactant.

In addition, at least one auxiliary nonionic surfactant is present inthe composition in a sufficient amount to increase the cleaning abilityof the principal nonionic surfactant. It is important to appreciate thatno irritating surfactants such as anionic surfactants are present in thecomposition of the present invention. Hence, there is no component ofthe composition of the present invention which is added to overcome orsuppress the irritating activity of a component. This results in anaturally inherent nonirritating surfactant composition.

Importantly, the auxiliary surfactants present in the composition areeffective for enhancing the cleaning ability of the principal auxiliarynonionic surfactant. In the instance where one auxiliary surfactant isused in conjunction with the principal nonionic surfactant, the cleaningability of the resultant composition is greater than the cleaningability of either the principal surfactant or the auxiliary surfactanttaken alone. More particularly, this occurs when both the principal andauxiliary nonionic surfactants comprise block polymers ofpolyoxyethylene and polyoxypropylene. Specifically, this enhancedcleaning activity occurs when the principal nonionic surfactantcomprises Pluronic® P85, (CTFA name: poloxamer 235) and the auxiliarynonionic surfactant comprises Pluronic® F87 (CTFA name: poloxamer 237).

The nonirritating detergent surfactant composition of the presentinvention further has extremely low irritation potential to ocular andperiocular tissue. The low irritation potential of the composition ofthe present invention may be demonstrated with in vitro Chinese hamsterovary cell cytotoxicity test. Specifically, when the principal andauxiliary nonionic surfactants are present in the nonirritatingdetergent surfactant composition in a combined amount of at most tenpercent by weight, and the composition applied to Chinese hamster ovarycells at a tenfold dilution, more than eighty percent of the cellssurvive.

BRIEF DESCRIPTION OF THE DRAWINGS

The advantages and features of the present invention will be betterunderstood by the following description when considered in conjunctionwith the accompanying drawings in which:

FIG. 1 is a three-dimensional representation showing the relativecleaning ability of compositions in accordance with the presentinvention having varying amounts of principal and auxiliary nonionicsurfactants; and

FIG. 2 is a plot of relative survival of Chinese hamster ovary cells forthe present invention, either unpreserved or preserved by five differentpreservative systems, showing the cytotoxicity profile thereof. Theprofile of an unpreserved anionic surfactant, disodium monolaurethsulfosuccinate, is also included for comparison.

DETAILED DESCRIPTION

It has been well established that a surfactant which cleans better isusually more damaging to cells. For example, anionic surfactants aregenerally more efficient in removing grease and dirt but are also moreirritating and have a high cytotoxicity profile.

Nonionic surfactants are known to be milder than anionic surfactants butheretofore have not demonstrated detergent activity on a par withanionic surfactants.

As hereinbefore briefly discussed, prior art formulations for lidhygiene have utilized anionic surfactants which have high cytotoxicityand irritation to sensitive surfaces. In combination with such ionicsurfactants, a number of components have been utilized in an attempt toreduce the irritant properties of the ionic surfactants. Because of theinherent irritant activity of anionic surfactants, compositionsincorporating such surfactants, even though compensating components arepresent, require complete and thorough rinsing of the compositions fromocular and periocular tissue due to the possibility of anionicsurfactant remaining in contact with such tissue after use of surfactantand thereby causing high irritation.

In view of the fact that no component of the composition of the presentinvention is inherently irritating to periocular or ocular tissue, norinsing of the composition following lid cleaning is required.

While the following description of the present invention is directed touse as cleansers for ocular and periocular tissue, because of itsnonirritating and low cytotoxicity profile, the composition of thepresent invention is also suitable for the cleaning of skin, mucousmembranes, wounds, contact lenses, and removal of makeup for eyes andfacial tissue. In addition, its use may be extended to the cleaning ofhands and fingers which would subsequently be in contact with eyes,wounds, or other sensitive areas.

The principal nonionic surfactant present in the composition of thepresent invention is a block copolymer of polyoxyethylene andpolyoxypropylene which are available under the trade name Pluronic®marketed by BASF. Specifically, the principal nonionic surfactant isPluronic® P85. A first auxiliary nonionic surfactant is also a blockcopolymer of polyoxyethylene and polyoxypropylene and specificallycomprises Pluronic® F87. The principal surfactant is present in thecomposition in an amount from about four percent to about nine percentby weight.

The first auxiliary surfactant is added to enhance the cleaning abilityof the principal surfactant which may be effected through bettersolubilization, emulsification, or wetting power. The preferredauxiliary surfactant, in accordance with the present invention,Pluronic® F87 is present in the composition in an amount from about 0.5percent to about two percent by weight.

Preferably, a second auxiliary nonionic surfactant, such as ethoxylatedoctyl phenol, may be combined with the principal and first auxiliarysurfactants. Specifically, the second auxiliary surfactant may beIgepal® CA 897 (CTFA name: octoxynol 40) marketed by Rhone-Poulenc.

Preferably, the total amount of surfactants in the composition of thepresent invention is ten percent or less of the total composition withthe remaining component being water. It should be appreciated that thecomposition of the present invention may be buffered by any commonbuffer system such as phosphate, borate, acetate, and citrate with thepH and osmolarity adjusted in accordance with well-known techniques toproper physiological values.

In addition, if a preservative is desired, the compositions may bepreserved with any well-known system such as benzyl alcohol with/withoutEDTA, benzalkonium chloride, chlorhexidine, Cosmocil® CQ, or Dowicil®200.

Importantly, because of the nonionic nature of the surfactants of thepresent invention, no chemical incompatability is encountered even if apositively or negatively charged preservative is incorporated, such asquaternary ammonium salts. This also applies to buffers and othermedicaments that may be used in combination with the composition of thepresent invention.

In addition, depending upon the use of the cleanser, amino acids,minerals, vitamins, or the like may be added to provide nutrition toskin or tissues. Further, moisturizers or emollients such asaloglycerine propylene glycol, hyaluronic acid, hydroxic propylcellulose, or carboxy methyl cellulose may be added to soothe the skin.Specifically, when the composition is to be used in connection withcleaning wounds, medications may be added, such as antibiotics,antimicrobiocidal agents, anti-inflammatory agents, local anesthetics,anti-acne agents, etc., depending upon the specific activity desired.

A clear advantage of the present invention resides not only in itsextremely low toxicity risk but also in its minimal chemicalincompatibility with other ingredients (such as preservatives, buffers,medications, etc.) incorporated in the formulations. The minimalchemically incompatible risk is attributed to the position of noionizable functional groups in the surfactants chosen in the presentinvention.

The cleaning ability, specifically the lipid cleaning ability, of thecomposition of the present invention is diagrammatically presented inFIG. 1 so as to illustrate the synergistic effect of nonionic surfactantcombinations which, in the case of Pluronic® F87 and Pluronic® P85,results in a greater cleaning ability than the cleaning ability ofeither the Pluronic® F87 or P85 taken separately. In addition, as willbe hereinafter demonstrated, the combination of the principalsurfactant, Pluronic® P85, and auxiliary surfactants, Pluronic® F87 andoctoxynol 40, provide lipid cleaning ability on a par with anionicsurfactants but with no irritating properties and significantly lesscytotoxicity.

The diagram as shown in FIG. 1 will be discussed in more detail afterthe following description of the protocol in determining the cleaningability of the detergent surfactant in accordance with the presentinvention.

In order to show lipid cleaning ability of the composition of thepresent invention, an artificial lipid mixture was utilized whichcomprised thirty percent cholesteryl stearate, thirty-five percentlanolin, and thirty-five percent Miglyol® 810 (CTFA name:caprylic/capric triglyceride).

This mixture was supported on a polymacon (38/0) lens (Hydron) with theconvex surface of the lens coated with the artificial lipid mixture bylightly touching the surface to the melted lipid and leaving the coatedlens on a slide (convex surface facing up), for between ten to thirtyminutes.

Thereafter, the composition to be tested was placed, five drops at atime, on the palm of a hand and the lens, with the convex surface facingdown, rubbed in a circular motion in the composition for twenty seconds.Thereafter, the lipid remaining on the lens was officially observed.

The cleaning efficacy scoring system was as follows:

    ______________________________________                                        CLEANING EFFICACY TEST                                                                  VISUAL OBSERVATION                                                  SCORE     (after rubbing lens with tested composition)                        ______________________________________                                        0         Lens is totally coated with lipid                                   1         1/6 of the lens is not covered by lipid                             2         1/3 of the lens is not covered by lipid                             3         1/2 of the lens is not covered by lipid                             4         2/3 of the lens is not covered by lipid                             5         5/6 of the lens is not covered by lipid                             6         All lipid on the lens is gone                                       ______________________________________                                    

The cleaning score, between 1 and 6, is plotted for various surfactantcompositions in FIG. 1 for percentages of principal surfactant from 0 to10%, first auxiliary surfactant from 0 to 10%, and second auxiliarysurfactant from 0 to 10%. The remaining composition is water.

These number scores appear in FIG. 1, which is diagrammaticallypresented in order to show the increased cleaning ability of thecomposition when the primary surfactant Pluronic® P85 is between about2% to about 9%, the first auxiliary surfactant Pluronic® F87 is presentin the amount of between 0.5% to about 2%, and the second auxiliarysurfactant octoxynol 10 is present in the amount of about 0.5% to about5%. Each of the points displayed in FIG. 1 include a total surfactantweight of about 10%. To compare the composition of the present inventionwith the prior art lid hygiene formulations, the cleaning efficacy test,as hereinabove described, was performed on I-Scrub, distributed bySpectra. The results are shown hereinbelow:

    ______________________________________                                        TEST SOLUTION    OBSERVED SCORE                                               ______________________________________                                        Spectra's I-Scrub                                                                              4.67,5.33,5,4.67,5.33                                                         Mean = 5.0, CV = 6.6%                                        The optimized    5.3,5                                                        formulation                                                                   ______________________________________                                    

These results demonstrate that the optimized formulation of the presentinvention has the equivalent cleaning ability as that of I-Scrub, whichis an anionic surfactant-based formulation.

The ingredients of I-Scrub are generally known as follows:

    ______________________________________                                        I-SCRUB                                                                       ______________________________________                                        Disodium monolaureth                                                                            anionic surfactant (mild,                                   Sulfosuccinate    high foaming)                                               PEG-200 Glyceryl Mon-                                                                           nonionic surfactant (emul-                                  otallowate        sifier, anti-irritant)                                      PEG-78 Glyceryl Mono-                                                                           nonionic surfactant (emul-                                  coccate           sifier, anti-irritant)                                      Cocoamidopropylamine                                                                            nonionic surfactant (foam                                   Oxide             booster, anti-irritant)                                     Benzyl Alcohol, EDTA,                                                                           preservative                                                Purified Water USP                                                            ______________________________________                                    

An important feature of the composition of the present invention is itslow cytotoxicity profile. The cytotoxicity was evaluated as follows toquantify chemically-induced toxicity. Chinese hamster ovary cells used(CHO) are a well-characterized cell line and are widely used incytotoxicity assays as has been well-documented in the literature.

The materials and methods of the present assay are as follows:

MATERIALS

A. CHEMICALS AND MEDIA

1. Ham's F-12 medium (1X, with sodium bicarbonate)

2. Heat inactivated fetal bovine serum (lots tested using SOP TC-003)

3. L-glutamine solution (200 mM)

4. Dulbecco's phosphate buffered saline (PBS)

5. Trypsin-EDTA solution (1X)

6. Sodium chloride

7. Sodium phosphate (monobasic and dibasic)

8. β-nicotinamide adenine dinucleotide phosphate (NADP)

9. Glucose-6-phosphate (Glc-6-P)

10. Potassium chloride

11. Magnesium chloride

12. Calcium chloride

13. Aroclor 1254 induced rat liver S9

14. Methanol

15. Giemsa stain

B. Tissue Culture Supplies and Cell Lines

1. Tissue culture dishes (6-well clusters)

2. Chinese hamster ovary (CHO) cells, clone K₁ -BH₄ (originally fromOakridge National Laboratory)

METHODS

A. Preparation

1. Media for cell growth (Ham's F-12)

a. Add 50 ml of heat inactivated fetal bovine serum per 500 ml Ham'sF-12 medium.

b. Add 2.5 ml of glutamine per 500 ml medium.

2. Liver 59--cofactors mix

a. Prepare stock solutions of: 0.M sodium phosphate, pH 8.0; 0.1M NADP;1.0M glc-6-P; 1.5M potassium chloride; 0.5M magnesium chloride; and 0.5Mcalcium chloride.

b. Prepare sterile 8.8 ml cofactor mix aliquots containing: 5.45 mldouble distilled water; 2.5 ml sodium phosphate; 0.4 ml NADP; 0.05 mlglc-6-P; 0.2 ml potassium chloride; and 0.2 ml magnesium chloride. Thesealiquots can be stored frozen at -70° C.

c. Prior to use, thaw aliquot cofactor mix and add 0.2 ml calciumchloride. A white precipitate will form.

d. Add 1 ml of liver S9 (-30 mg/ml) to the cofactor mix and store onice.

B. Cytotoxicity Assay

1. Trypsinize CHO cells using the procedures described in ResearchMicrobiology SOP TC-001.

2. Determine cell concentration using one of the procedures outlined inResearch Microbiology SOP TC-002.

3. Dilute the cell suspension to a final concentration of 100 cells perml in complete growth media. Maintain the cell suspension on ice untilcells are plated to minimize cellular attachment to the surfaces of thecontainer.

4. Pipet 2 ml of the cell suspension into each well (200 cells/well).Shake the dish in two directions immediately after filling all of thewells in the dish. This is critical to ensure even distribution of cellsthroughout the entire surface area of the dish.

5. Allow the cells to attach for 3 hours at 37°±1° C. in a humidifiedincubator with an atmosphere of 5% CO₂ in air.

6. At the time of treatment, change medium to 2 ml Ham's F-12 medium(with glutamine, without serum).

7. For assays designed to measure the effect of metabolic activation,add 0.4 ml of S9-cofactors mixture to 1.6 ml of Ham's F-12 (withglutamine, without serum) at the time of treatment.

8. Add test compound in 20 μl of ethanol, acetone or DMSO (1% v/v finalconcentration of solvent) depending on solubility. Note: DMSO alsofacilitates cellular uptake. if the test compound is a suspension (suchas liposomes) they can be added in up to 100 μl of PBS. Three wells areused per dose.

9. Each assay must include positive and negative controls. Theequivalent volume of the solvent alone serves as the negative control.Any known cytotoxic agents at cytotoxic doses can be used as positivecontrols (e.g., cyclohexamide, mitomycin C, benzo (a) pyrene).

10. Return dishes to the incubator for 3 hours. Do not stack the dishesmore than two high as it is important for sample cultures to stabilizeat 37°±1° C. at the same time. This is even more critical forexperiments involving S9 since the reaction kinetics for the enzymesinvolved in metabolic activation are temperature dependent.

11. Remove medium containing test compound out of each well and rinsesurface with 1 ml of PBS per well.

12. Pipet 2 ml of complete growth medium (Ham's F-12, with serum andglutamine) into each well.

13. Return dishes to incubator and allow cells to grow for 7-8 days. Donot handle dishes as this minimizes colony splitting.

14. Fix, stain and score colonies as described in Research MicrobiologySOP TC-005.

15. Express cytotoxicity data as cloning efficiency (C.E.) and relativesurvival (R.S.). ##EQU1##

The results of the cytotoxicity assay or cytotoxicity profile are shownin FIG. 2, which shows the relative survival of the Chinese hamsterovary cells as a function of concentration of the formulation tested.

The hereinabove-described CHO clonal assay was used to establish thecytotoxicity profiles for the present invention preserved by fivedifferent preservative systems. Ten to one hundredfold dilutions ofthese solutions were tested, with all dilutions being made in distilledwater. The unpreserved present invention was also tested. The vehicle,water in this case, was used as a positive control. The relative cellsurvival is calculated by comparing the cells surviving from aformulation with the cells surviving from water. Disodium monolaurethsulfosuccinate, a "mild" anionic surfactant commonly used in babyshampoos and lid hygiene products, was used as a negative control. Thesolutions tested were as follows:

1. Pluronic® P85/Pluronic® F87/octoxynol 40 (7:1:2 ratio) 10% solution

2. Pluronic® P85/Pluronic® F87/octoxynol 40 (7:1:2 ratio) 10%solution+Benzyl Alcohol (0.5%)

3. Pluronic® P85/Pluronic® F87/octoxynol 40 (7:1:2 ratio) 10%solution+Benzyl Alcohol (0.5%)+EDTA (0.05%)

4. Pluronic® P85/Pluronic® F87/octoxynol 40 (7:1:2 ratio) 10%solution+Benzyl Alcohol (0.5)+Germall 115 (0.3%)

5. Pluronic® P85/Pluronic® F87/octoxynol 40 (7:1:2 ratio) 10%solution+Dowicil® 200 (0.03%)-Phosphate Buffer

6. Disodium monolaureth sulfosuccinate

The results dramatically show the low cytotoxicity of the formulationsin accordance with the present invention. For example, at concentrationsof up to 10% of the unpreserved formulation in accordance with thepresent invention, an 80% relative survival is shown, which is roughly100 fold less cytotoxic than the "mild" surfactant, disodium monolaurethsulfosuccinate. The preserved formulations, depending on the preservatiesystem used, may be 30 to 100 fold less cytotoxic than disodiummonolaureth sulfosuccinate. Therefore, because of the low cytotoxicityof the formulations in accordance with the present invention, theformulation need not be rinsed, or flushed, from the eye afterinstillation. This is to be compared with prior art products comprisinganionic surfactants which must, because of their relatively highcytotoxicity, be rinsed, or removed, from the eye after instillationbecause residual anionic surfactant will cause eye irritation.

Hence, it can be readily appreciated that the low cytotoxicity of theformulation of the present inventions eliminates the criticality ofrinsing.

That is, if some, or all, of the formulation of the present inventionremains in the eye, little, if any, irritation occurs, due to thenonionic surfactants therein.

In addition, it is shown that a formulation in accordance with thepresent invention which is preserved with benzyl alcohol exhibited acytotoxicity profile similar to the unpreserved solution at 10% offormulation. Also, the addition of EDTA did not significantly alter thecytotoxicity profile of the formulation at 10%.

Other formulations of various preservatives exhibited a lowercytotoxicity profile.

The formulation of the present invention may be produced in anyconventional manner by combining the surfactants in the proportionshereinabove recited.

Although there has been hereinabove described a nonirritating detergentsurfactant composition suitable for application in cleaning of sensitivetissues such as periocular and ocular tissues, in accordance with thepresent invention, for the purpose of illustrating the manner in whichthe invention may be used to advantage, it should be appreciated thatthe invention is not limited thereto. Accordingly, any and allmodifications, variations, or equivalent arrangements which may occur tothose skilled in the art, should be considered to be within the scope ofthe present invention as defined in the appended claims.

What is claimed is:
 1. A nonirritating detergent surfactant compositionsuitable for application to and cleaning of sensitive tissue, saidnonirritating detergent surfactant composition comprising:a principalnonionic surfactant present in said nonirritating detergent surfactantcomposition in a sufficient amount to clean said sensitive tissue, saidprincipal nonionic surfactant comprising a block copolymer ofpolyoxyethylene and polyoxypropylene; a first auxiliary nonionicsurfactant present in said nonirritating detergent surfactantcomposition in a sufficient amount to increase the cleaning ability ofthe principal nonionic surfactant, said first auxiliary nonionicsurfactant comprising a block copolymer of polyoxyethylene andpolyoxypropylene; and a second auxiliary nonionic surfactant present insaid composition in a sufficient amount to increase the cleaning abilityof the principal nonionic surfactant, said second auxiliary nonionicsurfactant comprising an ethoxylated octyl phenol.
 2. The nonirritatingdetergent surfactant composition according to claim 1 wherein thecleaning ability of the nonirritating detergent surfactant compositionis greater than the cleaning ability of each of the principal andauxiliary nonionic surfactants.
 3. The nonirritating detergentsurfactant composition according to claim 1 or 2 wherein the cleaningability is the lipid cleaning efficiency of the surfactants.
 4. Anonirritating detergent surfactant composition having low cytotoxicityfor the cleaning of ocular and periocular tissue, said nonirritatingdetergent surfactant composition comprising:a principal nonionicsurfactant present in said nonirritating detergent surfactantcomposition in a sufficient amount to clean ocular and perioculartissue, said principal nonionic surfactant comprising a block copolymerof polyoxyethylene and polyoxypropylene; a first auxiliary nonionicsurfactant present in said nonirritating detergent surfactantcomposition in a sufficient amount to increase the cleaning ability ofthe principal nonionic surfactant, said first auxiliary nonionicsurfactant comprising a block copolymer of polyoxyethylene andpolyoxypropylene; and a second auxiliary nonionic surfactant present insaid composition in a sufficient amount to increase the cleaning abilityof the principal nonionic surfactant, said second auxiliary nonionicsurfactant comprising an ethoxylated octyl phenol.
 5. The nonirritatingdetergent surfactant composition according to claim 4 wherein thecleaning ability of the nonirritating detergent surfactant compositionis greater than the cleaning ability of each of the principal andauxiliary nonionic surfactants.
 6. The nonirritating detergentsurfactant composition according to claim 4 or 5 wherein the cleaningability is the lipid cleaning efficiency of the surfactants.
 7. Thenonirritating detergent surfactant composition according to claim 4 or 5wherein said principal and auxiliary nonionic surfactants are present insaid nonirritating detergent surfactant composition in a combined amountof at most 10% by weight and when applied to Chinese hamster ovarycells, more than 80% of the cells survive at ten fold dilution indistilled water.
 8. A nonirritating detergent surfactant compositionhaving low cytotoxicity for ocular and periocular tissue, saidnonirritating detergent surfactant composition comprising:a principal;nonionic surfactant present in said nonirritating detergent surfactantcomposition in a sufficient amount to clean said sensitive tissue, saidprincipal nonionic surfactant comprising a block copolymer ofpolyoxyethylene and polyoxypropylene; a first auxiliary nonionicsurfactant present in said nonirritating detergent surfactantcomposition in a sufficient amount to increase the cleaning ability ofthe principal nonionic surfactant, said first auxiliary nonionicsurfactant comprising a block copolymer of polyoxyethylene andpolyoxypropylene; and a second auxiliary nonionic surfactant present insaid composition in a sufficient amount to increase the cleaning abilityof the principal nonionic surfactant, said second auxiliary nonionicsurfactant comprising an ethoxylated octyl phenol, said principal andauxiliary nonionic surfactants enabling the combination of thesurfactant composition with positively or negatively chargedpreservatives, buffers and medicaments without chemical incompatability.